Dairy food intake has been associated with prostate cancer in previous work, and the ecologic correlation between milk intake and prostate cancer mortality may be stronger than for any other dietary factor, including total fat. The mechanism by which dairy increases risk is unknown but includes two possibilities. First, dairy may elevate circulating levels of insulin-like growth factor I (IGF-I), a likely risk factor for prostate cancer. Second, dairy calcium may suppress circulating levels of potentially cancer-protective 1,25-hydroxyvitamin D (1,25-D). Other evidence suggests a possible difference in a dairy effect on 1,25-D levels by ethnicity and vitamin D status. The proposed work will evaluate the two hypotheses as possible explanations for observed associations between dairy and prostate cancer risk. We seek to test the hypotheses that dairy intake increases IGF-I levels but reduces circulating 1,25-D levels, that the effects are mediated by measurable dietary factors in dairy, and that effects on 1,25-D levels differ by ethnicity and vitamin D status. The study population will include 545 men enrolled in the Fox Chase Cancer Center Prostate Cancer Risk Assessment Program (PRAP) from 7/00 to 6/07. Men are eligible if they are 35-69 years old, have no history of prostate cancer, and, for non-African American men, have at least one 1st-degree relative with prostate cancer; no family history is required for African American men, who make up about half of the sample, because of their already elevated risk. Upon enrollment, men provide a blood sample and complete diet and health history questionnaires. Laboratory analyses will include assessments of plasma levels of IGF-I, insulin-like growth factor binding protein-3, 25-hydroxyvitamin D, and 1,25-D. These will be examined in relation to dairy foods and nutrients of interest as potential mediators, such as protein, calcium, and other minerals. We will also examine possible effect modification of the dairy-1,25-D association by ethnicity and vitamin D status. Given the enormous implications of observing an adverse health effect for dairy foods, a better understanding of the mechanisms by which dairy might increase prostate cancer risk is essential, providing biologic evidence to support a simple but potentially controversial preventive strategy. Findings will also provide information critical to African Americans, for whom a recommendation to reduce dairy may be harmful rather than beneficial.